Biocidal Ceramic Compositions, Methods and Articles of Manufacture

ABSTRACT

The present invention provides biocidal ceramic compositions incorporating bioactive ionic species that are chemically bound in a substantially single-phase, crystalline, [NZP]-type structure, methods for producing the crystalline structures, and articles of manufacture incorporating the crystalline structures, and uses of the articles of manufacture. Bioactive ionic species can be, but are not limited to, Ag, Cu, Ni, Zn, Mn, Sn, Co, H, and combinations thereof.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a continuation application of U.S. patentapplication Ser. No. 11/450,034, filed Jun. 8, 2006, and titled“Biocidal ceramic compositions, methods and articles of manufacture,”which application claims the benefit of and priority to U.S. ProvisionalPatent Application Ser. No. 60/688,506, filed Jun. 8, 2005, and titled“Biocidal Ceramic Compositions, Methods and Articles of Manufacture,”and U.S. Provisional patent Application Ser. No. 60/803,703, filed Jun.1, 2006, and titled “Biocidal Ceramic Compositions, Methods and Articlesof Manufacture,” which applications are incorporated by reference hereinin their entireties.

GOVERNMENT LICENSE RIGHTS

The U.S. Government has a paid-up license in this invention and theright in limited circumstances to require the patent owner to licenseothers on reasonable terms as provided for by the terms of SBIR Phase IContract No. NBCHC050032 awarded by Homeland Security Advanced ResearchProjects Agency.

BACKGROUND OF THE INVENTION

1. The Field of the Invention

The present invention relates to crystalline, substantiallysingle-phase, ceramic compositions incorporating bioactive ionic speciesthat provide biocidal or antimicrobial properties, methods ofsynthesizing such ceramic compositions and methods for manufacturingmicrobe-destroying articles using the ceramic compositions and utilizingthem.

2. The Relevant Technology

The health and environmental hazards of bacterial contamination frommicrobes such as Eschericia coli and Salmonella commonly found in foodand water, Staphylococcus Aureus present in uncooked or undercookedmeat; Cryptosporidium parasites found in water, and other suchunicellular organisms, are no less than they have ever been in the past.In fact, with increasing human population, growing pollution and thepotential threats of bio-terror, microbial problems have assumed greaterdimensions in the present day and age.

For centuries, metals such as silver (Ag), copper (Cu), zinc (Zn), tin(Sn) and cobalt (Co) have been known to be benign antimicrobial agentsand have been used for various basic microbe-control applications. Mostof these applications utilized the antimicrobial metal in its unalloyedor alloyed form. However, in recent times, silver and copper, inparticular, have been used extensively in various other forms with othersubstances for disinfecting (antibacterial, antifungal and antialgal)applications. About 20 years ago, silver began being used with othermaterials for antimicrobial coatings, components and devices.

Different amounts of bioactive species have been incorporated intovarious organic, inorganic, composite and porous substrates tofacilitate antimicrobial activity or disinfecting properties. Typicalconventional uses of silver are based on physical admixing of silver orits compounds (e.g., silver iodide, nitrate, oxide, sulfadiazine) with acarrier for use in topical medications, dentistry and water treatment,or, depositing the mixture on a surface (e.g., colloidal coating, paste,or a glaze) on, for example, textiles, plastics, kitchen counters ortiles for floors and walls in restrooms. However, many of the prior artsilver-based compounds contain higher-than-needed levels of bioactive orantimicrobial dopants (Ag, Cu, Zn, etc.) and yet are not capable ofsustained, strong antimicrobial activity over a period of time.

In particular, where the antimicrobial species were physically bonded oradmixed with the base material or coated onto a substrate, theantimicrobial activity is likely to degrade rapidly resulting from lossof the antimicrobial (Ag, Cu, etc.) species due to dissolution ordegradation phenomena. Compared to the relatively unstable organic andcomposite biocides, inorganic biocides offer the advantages ofintrinsically higher environmental stability, safety (non-toxic) andcontrolled and prolonged antimicrobial activity.

State-of-the-art inorganic antimicrobials such as AgION™ and Zeomiccomprise silver (Ag) or copper (Cu) based zeolites (alumino-silicatebased minerals), wherein the silver or copper ions are put in place ofmetal ions in an open, skeletal network structure. However, in thisoften porous and open structure, both the host metal ions such as sodium(Na⁺), potassium (K⁺) and magnesium (Mg²⁺) and the dopant ions such asAg⁺ or Cu⁺ are very loosely held making them vulnerable to rapid,uncontrolled ion-exchange and acid leaching. Additionally, silver ionsin such zeolites can be easily reduced to metallic silver which couldtend to cause coloring of the antimicrobial material and, in turn, thehost object.

Alternative inorganic antimicrobial approaches include antimicrobialcompositions based on hydroxyapatite, zirconium/titanium/tin phosphate(such as Alphasan™) or silicon dioxide or titanium oxide or zinc oxide(Microfree™) crystalline chemistry. Several variations of the phosphatebased inorganic antimicrobial compositions exist, among which the mostexemplary are embodied in U.S. Pat. Nos. 5,296,238, 5,441,717 and5,698,229. For instance, in U.S. Pat. No. 5,296,238, microbicides covera family of phosphates represented by the general formula:

M_(a) ¹A_(b)M_(c) ²(PO₄)_(d) .nH₂O

wherein M¹ is silver, A represents at least one ion selected from thegroup consisting of hydrogen ion, alkali metal ions, and ammonium ion,M² is zirconium or titanium, n represents a number which satisfies0≦n≦6, a and b each represents a positive number and satisfies theequation 1a+mb=1, where 1 is valence of M¹ and m is valence of A, and cis 2 and d is 3.

While these prior-art microbicide (U.S. Pat. No. 5,296,238) andantimicrobial (U.S. Pat. No. 5,441,717) compositions represent some ofthe more physically and chemically stable inorganic materials withpotentially pronounced and prolonged antimicrobial activity to date,there are shortcomings associated with the intrinsic stability of theabove phosphate compositions. The stability issues arise from thepresence of monovalent alkali ions present at the A (or M¹) site, whichcreates reactivity and thermal expansion anisotropy issues. C. Y. Huang(Ph.D. Thesis, 1990) has computed and measured the thermal expansionanisotropies—the difference between axial thermal expansions in the ‘a’and the ‘c’ directions of the unit cell—of such compositions and clearlyshown the significantly higher anisotropy of the compositions withalkali metal ions (especially, Li⁺ and Na⁺) at the M¹ or A site ascompared to those with the larger alkaline earth ions such as Ca²⁺, Sr²⁺and Ba²⁺ at these sites.

Notably also, the disclosed synthesis methods for the microbicide andantimicrobial inorganic phosphate compositions of the prior-artdiscussed above involve: (a) corrosive reagents (chlorides, sulfates,oxynitrates, oxychlorides, etc.) that produce environmentally-unfriendlyeffluents; and (b) tedious chemistries—sometimes with more than oneiteration of digestion with carboxylic or dibasic acids such as oxalicand malic acid, pH-controlled reaction-precipitation, filtration,washing and controlled-drying.

SUMMARY OF THE INVENTION

Ceramic compositions of the present invention are particularly meant toovercome the existing limitations with the stability, reliability andlongevity of the state-of-the-art organically or inorganically-basedantimicrobial concepts. The present invention provides a way to overcomethe above deficiencies with the state-of-the-art and demonstratecrystalline, substantially single-phase, inorganic compositions withexcellent antimicrobial properties, environmental (physical, chemicaland thermal) stability and high melting temperatures (>1600° C.). Theinventive compositions belong to the family of crystalline ceramicscalled “[NZP]”, which encompass numerous sub-families.

By the present invention unique, crystalline, [NZP]-type, inorganicbiocidal compositions containing bioactive ions such as, but not limitedto, silver, copper and zinc that are chemically-bound in a single-phasecrystal structure and yet exhibit excellent antimicrobial attributes bymeans of controlled ion-exchange or rapid killing mechanisms, andmethods to make and use the compositions, are provided. These ceramicbiocidal compositions are synthesized with a processing step thatincludes heat treatment at temperatures >900° C., as a result of whichthe inventive compositions are inorganic, crystalline and have excellentphysical (color, dimensional and microstructural stability), chemical(non-reactive, non-leaching, non-toxic and uniformly bioactive) andthermal (temperature and radiation resistance, low expansion, thermalshock resistant) properties.

Broadly, [NZP] ceramics are represented by the chemical formulaNaZr₂(PO₄)₃ or NaZr₂P₃O₁₂ and characterized by a very unique crystalstructure that comprises a three-dimensional skeletal network of PO₄tetrahedra and ZrO₆ octahedra which are corner-linked together by sharedoxygen atoms. The [NZP] structure is exceptionally flexible towardspartial or complete ionic substitution at various lattice sites.[NZP]-type ceramics with alkaline-earth ions substituted at the sodium(Na) site, such as CaZr₄P₆O₂₄, SrZr₄P₆O₂₄ and BaZr₄P₆O₂₄ and certainsolid-solutions of the same are significantly more physically,chemically and thermally stable, and mechanically durable than the basic[NZP] compositions with alkali ions at the sodium site (such asNaZr₂P₃O₁₂, Ag_(0.05)Na_(0.95)Zr₂P₃O₁₂, etc.).

With the above in mind, the materials aspect embodied in the currentinvention creates novel, crystalline, single-phase, [NZP]-type biocidalcompositions which have superior environmental and color stability, hightemperature resistance (greater than 1250° C.) and relatively moreisotropic structural properties to complement their excellent andreliable antimicrobial performance over prolonged periods compared tothe state-of-the-art.

Specifically, the novel biocidal compositions involve: (a) suitablecombinations of alkaline earth (Ca²⁺, Ba²⁺, etc.) and bioactive (Ag+,Cu⁺ or Cu²⁺, Zn²⁺, etc.) ionic substitutions at the sodium (Na) sitesand, optionally, any appropriate partial or complete ionic substitutionsat other sites, especially the phosphorus (P) site; and (b) any suitablecombinations of alkali metal (Na⁺, K⁺), alkaline earth (Ca²⁺, Ba²⁺,etc.) and bioactive (Ag+, Cu⁺ or Cu²⁺, Zn²⁺, etc.) ionic substitutionsat the sodium (Na) sites and, necessarily, appropriate partial orcomplete ionic substitution(s) especially at the phosphorus (P) site.

The synthesis process used to make the crystalline, biocidalcompositions of this invention involves less corrosive and hazardousreagents (e.g., carbonates, nitrates, hydroxides and oxides) and, as anadded advantage, takes a simpler and direct reaction-precipitationapproach followed by calcination (heat-treatment) of the driedprecipitate at temperatures between 900° C. and 1200° C.

Overall, the inventive crystalline compositions, by virtue of the myriadways of doping them with bioactive elements and myriad forms into whichthey can be made, offer remarkable versatility of use for applicationsranging from disinfection of water and contaminated fluids tomicrobe-proofing of food items and packages, construction materials,textiles and rubber, home and industrial appliances, medical devices,and space suits to enabling catalytically-enhanced oxidation of sootparticles in diesel particulate filters (DPFs).

These and other embodiments of the present invention will become morefully apparent from the following description and appended claims, ormay be learned by the practice of the invention as set forthhereinafter.

BRIEF DESCRIPTION OF THE DRAWINGS

To further clarify the present invention, a more particular descriptionof the invention will be rendered by reference to specific embodimentsthereof which are illustrated in the appended drawings. It isappreciated that these drawings depict only typical embodiments of theinvention and are therefore not to be considered limiting of its scope.The invention will be described and explained with additionalspecificity and detail through the use of the accompanying drawings inwhich:

FIG. 1 shows an X-ray diffraction analysis pattern corresponding to oneof the crystalline, single-phase [NZP]-type, biocidal Type (I) ceramiccompositions.

FIG. 2 illustrates a flow chart of the sequence of processing steps forsynthesizing the inventive ceramic compositions into powder form usingthe environmentally-safer, reaction-precipitation based wet-chemicalapproach, according to one aspect of the present invention.

FIG. 3 is a photograph which clearly illustrates the results of anantimicrobial assay test involving some of the inventive biocidalceramic compositions and their ability to destroy or prevent the growthof Escherichia Coli bacteria.

FIG. 4 summarizes the results of antimicrobial testing of small couponsamples of: (a) selected inventive biocidal ceramic compositions; and(b) control samples (gauze and dry wall) and bears clear evidence of theexcellent microbe-destroying properties of most of these compositions incontrast to the control samples, which are ineffective.

DETAILED DESCRIPTION OF EXEMPLARY EMBODIMENTS

The present invention relates to biocidal, crystalline, [NZP]-typeceramic compositions having an effective amount of active speciesincorporated in the crystal structure to form substantially single-phasecompositions (hereinafter, referred to as “ceramic compositions” or“single-phase compositions”), methods for producing such ceramiccompositions, as well as uses for the ceramic compositions of thepresent invention. As used herein, the term “substantially single-phasecomposition” refers to the incorporation of the bioactive agents intothe crystalline ceramics such that chemical bonding of the bioactiveagent occurs at the atomic level with the crystalline structure. One waythis is represented is that single-phase compositions have chemicalformulas such as ‘Ca_(1-x)Ag_(2x)Zr₄P₆O₂₄’ where ‘x’ can assume valuesfrom 0 to 1, whereas multi-phase compositions have chemical formulasdenoted as, for example, Ag₂O+SiO₂, AgNO₃+TiO₂, Ag+HAP, etc. FIG. 1shows the X-ray diffraction pattern of an inventive single-phasecomposition with chemical formula Ca_(0.9)Ag_(0.2)Zr₄P₆O₂₄.

Chemically bonding the antimicrobial element to the ceramic crystalstructure extends the antimicrobial life of the material since thechemical bond increases the retention of the bioactive agent within theceramic structure and prevents leaching of the element therefrom astypically occurs in many of the prior art ceramic materials havingsilver or silver-based anti-microbial agents. In some of the prior art,antimicrobial elements could be leached away by the environment, forexample via hot water, dilute hot acids and alkalis or deteriorate dueto significant heat. In these prior art compositions, when exposed toheat, the silver could dissociate from the host carrier or matrix(especially, in the case of polymeric hosts such as resins, nylon,polyester, polyurethane, etc.) that decomposes, ablates or melts away.Therefore, in single-phase compositions, the bioactive agent isessentially locked in the chemical structure reducing its ability to beremoved from the ceramic composition, except by selective and controlledion-exchange, and maintaining its effectiveness over even longer periodsof time than is possible in the prior art.

The ceramic compositions of the present invention relate to a largefamily of ceramics generally known as [NZP]s whose crystal structuresare characterized by a three-dimensional network of corner-linkedpolyhedra (PO₄ tetrahedra and ZrO₆ octahedra) having rhombohedral ormonoclinic crystal symmetries.

Generally, the ceramic compositions of the present invention, will havea single-phase crystalline structure. For example, those of skill in theart will understand that individual [NZP]-type crystallites inherentlyalways has a single-phase structure. However, when the [NZP]-typeceramic compositions are synthesized, all of the bioactive species maynot necessarily react to form the single-phase ceramic composition.Thus, compositions of the present invention have at least 90% of thebioactive species chemically bound to the single-phase crystallinestructure, preferably at least 95% of the bioactive species chemicallybound to the single-phase crystalline structure, even more preferably atleast 99% of the bioactive species is chemically bound to thesingle-phase crystalline structure. Also, in spite of the use of highpurity raw materials, it is possible that a small portion of thereactants may stay unreacted or partially reacted and present themselvesas separate phases. Based on X-ray diffraction analysis, it has beendetermined that a nominally phase pure [NZP] composition, in crystallinepowder form, still has about 5.0 volume % of non-[NZP] phases. In spiteof the small amounts of non-[NZP] phases, many [NZP] compositions haveexcellent chemical and thermal stability, and melting points in excessof 1500° C. For the purposes of clarity, as used herein, the term“substantially single-phase” accounts for possible situations whereextraneous phases may appear in the [NZP] compositions, whether they arein as-synthesized powder form or as-processed bulk articles.

A unique and extremely advantageous feature of the [NZP] structure isthat it is exceptionally flexible towards partial or complete ionicsubstitutions at various lattice sites. The chemical formula for thebasic or parent [NZP] composition is NaZr₂P₃O₁₂ and a generalizedformula representing the stoichiometry of such [NZP] compounds is M¹M²A₂^(VI)P₃ ^(IV)O₁₂, where M¹ is typically referred to as “sodium” site andM² notates any substitutions for or excess additions at the M¹ site. Ifthe valency of the cation occupying the M¹ site is ‘2’ (alkaline earthion), then the general formula becomes M¹M²A₄ ^(VI)P₆ ^(IV)O₂₄, where M²represents substitutions or excess additions to the M¹ site.

The inventive ceramic compositions herein are represented by thefollowing general chemical formulas where M², A and B represent therespective ionic substitutions at the parent M¹, Zr (zirconium) and P(phosphorus) host sites of the [NZP] structure:

(I) M¹ _(1-x-1y-mz)M² _(kx)Zr^(VI) _(4-y)A_(y)P^(IV) _(6-z)B_(z)O₂₄where ‘M¹’ can be one or more divalent alkaline earth cations such asMg, Ca, Sr, Ba, or a stoichiometric combination thereof ‘M²’ can be anybio-active element such as, but not limited to, H, Ag, Cu, Ni, Zn, Mn,Co, or a stoichiometric combination thereof, and x, y, z, k, l, and mare governed by the following mathematical rules:

-   -   (i) 0<‘x’≦1, 0≦‘y’≦4, and 0≦‘z’≦6;    -   (ii) ‘k’=1 if ‘M²’ is a divalent cation such as Cu²⁺, Ni²⁺,        Zn²⁺, and the like, or a stoichiometric combination thereof;    -   (iii) ‘k’=2 if ‘M²’ is a monovalent cation such as Ag⁺, Cu⁺, and        the like, or a stoichiometric combination thereof;    -   (iv) ‘1’=0.5 or 0 or −0.5, respectively, depending on whether        ‘A’ is pentavalent (such as, but not limited to, Nb⁵⁺, Ta⁵⁺,        V⁵⁺, and pentavalent lanthanide metals) or a tetravalent (such        as, but not limited to, Ti⁴⁺, Hf⁴⁺, and tetravalent lanthanide        metals) or a trivalent (such as, but not limited to, Y³⁺, Sc³⁺,        and trivalent lanthanide metals) cation; and    -   (v) ‘m’=0.5 or 0 or −0.5 or −1, respectively, depending on        whether ‘B’ is hexavalent (such as S⁶⁺) or pentavalent (such as        As⁵⁺) or tetravalent (such as Si⁴⁺, Ge⁴⁺) or trivalent (such as        Al³⁺, B³⁺) cation;

(II) M¹ _(1-x-y-mz)M² _(kx)Zr^(VI) _(2-y)A_(y)P^(IV) _(3-z)B_(z)O₁₂,where ‘M¹’ is one or more monovalent alkali cations such as Li, Na, K,Rb, Cs, or a stoichiometric combination thereof, ‘M²’ can be anybio-active element such as, but not limited to, H. Ag, Cu, Ni, Zn, Mn,Co, or a stoichiometric combination thereof, and x, y, z, k, l, and mare governed by the following mathematical rules:

-   -   (i) 0≦‘x’≦1, 0≦‘y’≦2, and 0≦‘z’≦3;    -   (ii) ‘k’=0.5 if ‘M²’ is a divalent cation such as Cu²⁺, Ni²⁺,        Zn²⁺, and the like, or a stoichiometric combination thereof;    -   (iii) ‘k’=1 if ‘M²’ is a monovalent cation such as Ag⁺, Cu⁺, and        the like, or a stoichiometric combination thereof;    -   (iv) ‘l’=1 or 0 or −1, respectively, depending on whether ‘A’ is        pentavalent (such as, but not limited to, Nb⁵⁺, Ta⁵⁺, V⁵⁺,        pentavalent lanthanide metals) or a tetravalent (such as, but        not limited to, Ti⁴⁺, Hf⁴⁺, tetravalent lanthanide metals) or a        trivalent (such as, but not limited to, Y³⁺, Sc³⁺, trivalent        lanthanide metals) cation; and    -   (v) ‘m’=1 or 0 or −1 or −2, respectively, depending on whether        ‘B’ is hexavalent (such as S⁶⁺) or pentavalent (such as As⁵⁺) or        tetravalent (such as Si⁴⁺, Ge⁴⁺) or trivalent (such as Al³⁺,        B³⁺) cation.

Exemplary formulas according to the above general formulas include, butare not limited to, Ca_(0.9)Ag_(0.2)Zr₄P₆O₂₄ andSrNi_(0.1)Zr_(3.9)Y_(0.1)P_(5.9)Si_(0.1)O₂₄ from Type (I) ceramics, andKNi_(0.1)Zr₂P_(2.8)Si_(0.2)O₁₂ and NaAgZr₂P₂SiO₁₂ from Type (II) ceramiccompositions.

One important aspect of this invention is the ionic-doping of theceramic compositions with effective amounts of a bioactive agent usuallysubstituting at the appropriate sites (as discussed earlier) of the[NZP]-type crystal structure. The bioactive agent can be a bioactiveantimicrobial element, e.g., for killing bacteria, microbes, or algae,or may have another property, such as a catalytic or chemical conversionproperty. In one embodiment, bioactive agents include but are notlimited to, Ag, Cu, Zn, Ni, Mn, Co, or other metallic elements. Inaddition, the bioactive agent could potentially be hydrogen (H). Thebioactive agent can be incorporated in various concentrations, forexample, in amounts of about 0.0001 to about 20.0 wt % of thesingle-phase ceramic composition. In another important embodiment, the‘A’ atoms substituting at the octahedrally-coordinated (VI) zirconium(Zr) sites, can include lanthanide metals. Another noteworthy embodimentis that, where the phosphorus (P) ions at the tetrahedrally-coordinated(IV) phosphorus site themselves can have antimicrobial activity, thisadds to the antimicrobial activity of the ceramic composition as awhole. However, doping the ceramic composition with any bioactive agentas described above has a synergistic effect above and beyond theinherent antimicrobial activity of the inorganic complex-phosphatematerial itself

Because the M sites can be adjusted to have various alkali or alkalineearth elements, different elements (ions) can be substituted and thecompositions can be tailored appropriately for each application. Forexample, in one embodiment of the present invention, the M¹ site can becalcium (Ca). Calcium-based ceramics, especially phosphates, are uniquebecause they are extremely biocompatible. Therefore, bio-applicationsinvolving the human body and life-sustaining utilities, may becalcium-based, single-phase [NZP]-type compositions such as, but notlimited to, Ca_(0.95)Ag_(0.1)Zr₄P₆O₂₄. The relevant bio-applicationscover a broad range from medical devices such as, but not limited to,catheters, feeding tubes, woundcare ointments, dental cements, andnon-biofouling membranes for disinfection of drinking water orwastewater.

However, any or all of M (alkali or alkaline earth), Zr (zirconium)and/or P (phosphorus) sites can be manipulated to engineer single-phase[NZP] or [NZP]-type compositions with desirable properties. For example,for applications where a stronger and more thermally stable, UV-stable,and/or mechanically stronger bioactive ceramic material is desired,barium-based polycrystalline, single-phase compounds, such as, but notlimited to, Ba_(1.3)Zr_(3.9)Co_(0.1)P_(5.6)Si_(0.4)O₂₄, may be morepreferred—where, the bioactive element is ‘Co’. As such, the ceramiccompositions can also be modified as desired to increase their stabilityand to have enhanced chemical properties.

In another useful embodiment of the invention, silicon (‘Si’)substitution of the P^(IV) site can substantially improve theenvironmental (due to moisture, salts, reducing agents, etc.) anddiscoloration resistance of the ceramic compositions. For instance, aceramic composition having the formula KAg_(0.1)Zr₂P_(2.9)Si_(0.1)O₁₂ isexpected to have better environmental and color stability than, forexample, K_(0.9)Ag_(0.1)Zr₂P₃O₁₂ especially at higher temperatures andin the presence of light or radiation. A few common and importantfeatures of the ceramic compositions, especially those withsilica-substitution, of the present invention is that they are insolublein water and non-polar solvents, chemically inert against corrosivespecies such as acids, alkalis and salts to temperatures greater than100° C., stable up to very high temperatures in air (at least 1400° C.),and, more notably, substantially harmless to the surrounding environment(human bodies, animals, plants, etc.).

Yet another exemplary embodiment of the invention is producingsingle-phase crystallites which can be formed into various morphologiessuch as powders (e.g., particulates and grains), whiskers, fibers, andthe like, such that the bioactive agent is incorporated substantiallyevenly throughout the crystalline structure and across all crystallites.The present invention allows for doping the ceramic composition in amore homogeneous or uniform manner than was possible in the prior art.The ceramic crystallites have a substantially uniform concentration ofbioactive agent throughout so that in any cross section of the ceramicbody the antimicrobial effectiveness is virtually the same. As such, auser of a bulk structure or product formed from ceramic crystallites ofany given composition and in any application, especially inbio-applications, can be assured of effectiveness across the entirestructure. For example, where the ceramic crystallites are formed into abulk object such as a monolithic water purifier or filter, the entirestructure will have substantially the same biological activitythroughout so that portions of water will not go untreated or lesstreated. Moreover, the presence of controlled porosity increases thesurface available for biocidal activity. Thus, where ceramic structuresof the present invention include bioactive agents, the monolithicceramic structures have the highly desirable properties of isotropic,stable, controlled and prolonged ion-exchange based antimicrobialcharacteristics.

The ceramic compositions of the present invention are amenable tovarying and/or controlling the doping levels of the bioactive agent(s).Depending on the application, a higher concentration of bioactive agentmay be desired. For example, in waste water treatment facilities wherewater flow rates and volumes are relatively high, the concentration ofthe antimicrobial agent (such as silver ‘Ag’) in the water filters maybe higher than for filters for point-of-service water purifiers, forexample, tap water. A combination of bioactive agents may also bedesired. For instance, in wastewater filtration applications, it mayalso be desirable to control the growth of algae. Accordingly, theceramic compositions may have, for example, both silver (‘Ag’) andcopper (‘Cu’) as bioactive agents present in the single-phase [NZP]structure.

Another manifest advantage of the biocidal ceramic formulations of thepresent invention is that the formulations are also capable ofdestroying microbes virtually upon contact—referred to as “pseudocontact-killing”. This occurs when a sufficiently high concentration ofvery-finely dispersed sub-micron or nano-sized grains of theantimicrobial [NZP]-type composition is utilized, whether in the form ofa mixture with a non-leachable organic or inorganic carrier, or as in acoating layer on the surface of any article or device, or asincorporated into a bulk object made from the antimicrobial compound. Atoptimum grain size, concentration and type of bioactive agents, theresulting rapid rates and larger surface of activity of the ion-exchangebased microbe destruction process produces substantially the sameeffects as contact-killing.

Various synthesis techniques based on wet-chemical methods such assol-gel, and hydrothermal synthesis, and dry techniques such as solidstate reaction (or oxide-mixing) can be used for making the inventiveceramic compositions. For example, in the sol-gel synthesis embodiment,the raw materials employed are water soluble salts (e.g., chlorides andnitrates) of alkali or alkaline earth element(s) and the bioactiveelement(s) like silver, copper and zinc, zirconium complexes such aszirconium oxychloride, (ZrOCl₂.xH₂O) and oxynitrate (ZrO(NO₃)₂.xH₂O),and ammonium dihydrogen phosphate (NH₄H₂PO₄) or phosphoric acid (H₃PO₄).As desired, predetermined and controlled amounts of silicon ions can beintroduced in place of phosphorus ions, by mixing the aqueous solutioncontaining the alkali/alkaline earth species and Zr⁺⁴ ions with silica(SiO₂) sol followed by addition of a solution containing phosphorusions. Upon addition of the phosphorus containing species, a gel-likeprecipitate results. The precipitate is dried in air at 100° C. for 24hrs. and then crushed and ground using a mortar and pestle, or othersuitable methods, to yield fine agglomerated powder. The fine powder isthen calcined at temperatures between 750° C. and 1050° C. for about5-10 hours to obtain crystalline, single phase [NZP]-type antimicrobialcompositions.

The hydrothermal technique, a technique similar to that used forsol-gel, can be used to produce precursor powders of the inventivecompositions which are then treated hydrothermally under controlled pHconditions to obtain single phase ceramic compositions, for example,Ca_(0.95)Ag_(0.1)Zr₄P₆O₂₄. As in the case of the sol-gel method, toensure complete crystallinity and single-phase nature of thecompositions, post-heat treatment (between 800° C. and 1000° C.) of thehydrothermally-derived powders may be necessary.

In utilizing the solid-state oxide reaction synthesis process, differentprecursors may be used. In one embodiment, for Type (I) compositions, astoichiometric mixture of zirconates of the alkaline-earth metal alongwith oxides, carbonates or hydroxides of the bioactive elements,zirconium pyrophosphate (ZrP₂O₇) and silica (SiO₂) can be used to obtainsingle-phase compositions such asBa_(1.3)Zr_(3.9)Co_(0.1)P_(5.6)Si_(0.4)O₂₄ through solid-state mixingand reaction calcination at temperatures as high as 1200° C. For optimumresults from the solid-state calcination process, the precursors shouldbe mixed thoroughly for which any suitable method may be used. In oneadvantageous embodiment, grinding is performed by ball milling withceramic grinding media for convenience and reliability.

One preferred and beneficial embodiment of the processing approach(es)to synthesize the inventive ceramic compositions involves a simple, moreenvironmentally-safe reaction-precipitation approach, in which thepreferred chemical reagents: are carbonates, nitrates, acetates,hydroxides or oxides, any of which can be used as a raw material sourceto provide the alkali, alkaline earth, bioactive species, and/or thezirconium or species substituting for the zirconium site. In addition,chemical reagents can include phosphoric acid (H₃PO₄) or ammoniumdihydrogen phosphate (NH₄H₂PO₄) that can be used as a raw material toprovide the phosphorus species. Colloidal silica can be used whensilicon substitution of phosphorus in the ceramic compositions istargeted. All chemical reagents, except the phosphate species, are firstintimately mixed into a slurry with finely divided solids dispersed inan aqueous medium. Intimate mixing is accomplished with the help ofceramic grinding media and suitable mixing action such as rolling orvibration. The calculated amount of phosphoric acid or ammoniumdihydrogen phosphate, preferably at a temperature between 35° C. and 40°C., is then slowly added to the aqueous slurry accompanied by steadystirring of the reaction mix. After reaction, fine inorganicprecipitates, with a paste-like consistency, of the respective ceramiccompositions are formed. This paste is dried at about 100° C. for about24 hours or until completely dry. The dried amorphous orpartially-crystalline precipitates are calcined (heat-treated) between900° C. and 1200° C. (depending on composition) to obtain crystallineand single-phase compositions. A flow chart of thereaction-precipitation processing approach related to the inventivecompositions is provided in FIG. 2. As can be noted, this process issimilar to the sol-gel approach except that it utilizes fine dispersionsor colloids instead of sols (solutions) for the reactants. Single phaseand crystalline nature of the compositions is verified using X-raydiffraction (as shown in FIG. 1) analysis and particle densitymeasurements followed by comparison with theoretical values.

Since the biocidal ceramic compositions of the present invention areexpected to show excellent antimicrobial properties in addition to beingphysically, chemically and thermally very stable, appropriate testingwas undertaken to demonstrate the same. To test the biocidal propertiesof the inventive compositions, conventional or modified assays based onAATCC or EPA protocols can be adopted. Whether in aqueous powderformulations or as bulk test samples, log kill rates after 24 hours testexposure with respect to Salmonella cholerasuis and (or) other commonlyfound harmful microbes such as Escherichia coli and Staphylococcusaureus need to be adequately high. Log kill rates of greater than 1.0 or2.0 using standard antimicrobial assay procedures are considered to behigh enough for various applications in the field. As discussed indetail in Examples 2 and 4 (below), the log kill rates of the inventiveconcepts were measured to be exceptionally high compared to variousstate-of-the-art antimicrobial concepts. As provided in the examples,all the [NZP]-type biocidal compositions (in powder or bulk form) of thepresent invention exhibit log kills rates of at least 1.0 with respectto Salmonella cholerasuis and Escherichia coli under standard assaytesting. In another embodiment, in the same tests, several [NZP]compositions exhibited extremely high log kill rates of over 5.5,reproducibly. In yet another embodiment, the log kill rate for a few ofthe inventive [NZP]-type compositions is about 1.0 to about 7.0,preferably up to about 7.0. In addition, Example 5 below establishesnon-leaching, non-discoloring and environmental resistancecharacteristics of the ceramic compositions.

The ceramic compositions of the present invention can be veryadvantageously utilized for antimicrobial applications in variousmaterial forms. As used herein, the term “material” covers anymorphology wherein substantially the entire morphology comprisescrystallites of the inventive ceramic composition. Thus, materials ofthe present invention can include, but are not limited to, powders, bulkobjects, and the like, that incorporate crystallites according to thecompositions of the present invention, wherein the crystallites aresubstantially single-phase. In one embodiment, crystallites can bemanufactured directly in powder form, and utilized in powder-ladenplastics or rubbers, powder-mixed fertilizers or other chemicals,powder-containing cosmetics and dispersions, powder-containing papers,and powder-coated textiles. In another embodiment, when powders of thebiocidal compositions are mixed with appropriate organic and inorganicdispersants (phosphates, sulfonates, polyacrylates, etc.) and binders(silicates, glycols, starches, and the like) to produce paintable orsprayable mixtures they can be conveniently and beneficially utilizedfor coating the interior of buildings, walls, home and officefurnishings, sewer or storm drain pipes, textiles and apparel, leatherand sporting goods, filters for water or air or gases, packages for foodand other perishables, bones and cartilages etc. Powder-based coatingsare also capable of being applied to various large substrates orsurfaces ranging from kitchen, bathroom or masonry tiles to exteriors ofbuildings and bridges, automobiles, aircraft and marine vehicles usingsuitable techniques ranging from glazing and sputtering to combustionand plasma spray processes.

It is also a notable aspect of this invention that the size of thegrains in the powder can be modified to include nano-sized particles,which enables the realization of thin-film coatings with rapid microbialdestruction (pseudo contact-killing) properties that are advantageousand appropriate for bones and cartilages, medical devices, clean-roomfacilities in hospitals and electronics, and space-suits and otherspace-related modules that must be protected from microbialcontamination. On the other hand, large-grained powders (resembling sandor grog or, even small rocks) of the inventive biocidal ceramiccompositions have great applicability in disinfection treatment ofcontaminated liquid streams, particularly so, for waste-water anddrinking water. The powder form of the respective compositions includesany suitable morphologies such as, but not limited to, platelets,whiskers, fibers, and the like, depending on the particular applicationfor which they will be used.

In another aspect of the utility of this invention, appropriately sizedand shaped single-phase ceramic compositions can be used asantimicrobially-active fillers or sealants admixed with: (1) organicmaterial carriers such as, but not limited to, natural or syntheticresins, epoxies, plastics, polymers, rubber, wood pulp, etc.; or (2)inorganic carriers comprising various cements (natural, Portland,dental, and such), plasters (gypsum, dolomite, etc.), resins(polysilzanes, polycarboxysilazanes, etc.) and substrates (glassymatrices, silica or other aerogels, zeolites, activated charcoal, etc.);or (3) in mixtures of any of the above organic and inorganic carriers.

For producing bulk components from the single-phase biocidal ceramiccompositions, any known shape forming technique such as die and isopressing, slip casting, extrusion, and injection molding can be used.All green bodies are subjected to carefully controlled drying,debindering, and sintering schedules—with the schedules having adependence on size, shape and desired final properties of the bulkarticle. In general, in the bulk article processing approach,pre-qualified powders of the inventive compositions are milled orscreened to obtain a particle size distribution that is appropriate forthe process. Organic or inorganic surfactants and binders such as, butnot limited to, polyacrylates, sulfonates, sodium silicate, stearicacid, paraffin wax, polyethylene glycol (PEG), polyvinyl buterol (PVB),and polyvinyl alcohol (PVA) are added in the amounts of a few weightpercent based on solids to improve the formability and green strength ofthe component. The material is then cast or formed into a desired shape.

Using the above methods or other methods understood to those of skill inthe art, ceramic structures can be formed in myriad sizes and shapes.Alternatively, sizing and shaping of the ceramic structures can be partof an additional step subsequent to forming and sintering the bulkceramic structure. A specific instance of a post-processing step ismachining. Typically, the bulk ceramic object is formed and consolidatedto a shape and size that are as close to final requirements as possibleand then machined to exact final shape and size. As will be appreciated,the potential uses of bulk ceramic structures based on the biocidalcompositions of the present invention are many. Among the many ceramicobjects producible, one of the more desired embodiments forantimicrobial application is that of a water filter. The use of ceramicfilters has been found to be significantly more advantageous. Ceramicfilters have the intrinsic properties of non-toxicity, corrosionresistance, high temperature resistance, ability to handle largepressure drops, diminished fouling, excellent control of porosity andpore size distribution, and rigidity to allow manifolding.

Depending on the design and functionality of the filter, its shape andsize can vary from a simple circular disk about 7.62 cm (about 3 inches)in diameter by about 0.635 cm (about 0.25 inches) thick to a complex,multichannel rectangular or tubular shape several centimeters in crosssection and tens of centimeters in length. Typically, the simpledisk-shaped ceramic filters can be formed by pressing appropriatepowders of the ceramic composition mixed with a suitable amount ofbinder and/or fugitive binder in a die under a uniaxial hydraulic pressat about 40 to 55 MPa pressure, followed by cold isostatic pressing atabout 200 MPa. After the isostatic pressing, the component is heatedslowly in a furnace up to the binder burnout temperature and thenfurther up to the sintering temperature anywhere between 1400° C. to1600° C. for several hours to densify the ceramic to required levels andretain porosity appropriate for filtration purposes. Relatively morecomplex-shaped, larger filters can be fabricated using wet-methods suchas slip casting and pressureless sintering. Aqueous slip-casting is acost-effective, manufacture and environmental-friendly process thatyields objects with uniform physical, chemical and mechanicalproperties.

Another uniquely beneficial aspect of this invention is that filters(for fluids such as, but not limited to, water and gases) made out ofthe inventive antimicrobial ceramic compositions can be made tosimultaneously and advantageously perform microbial decontamination(biological purification) and ultrafiltration (physical purification).Knowing the excellent antimicrobial properties of the inventive ceramiccompositions and having the ability to form a chemically inert,non-leaching filter body of any desired shape and size, it is then onlya matter of tailoring the porosity in the surface and bulk of the filterbody so that it enables ultrafiltration without reducing the efficiencyof the filtration process. Therefore, two advantageous results of theapplication include a high surface-to-volume ratio filter design, andadequate physical and mechanical properties of the filter.

To obtain the dual-purpose, high performance filter geometries from theceramic compositions of this invention, the microstructure and porosityaspects of the filter body can be carefully controlled. It has beennoted that introducing porosity whose nominal size ranges from about 0.5to about 0.9 microns makes the filter “bacterially-safe” and,furthermore, “bacterially-sterile” when the pores are nominally betweenabout 0.2 to about 0.5 microns. In one embodiment, the porosity of theceramic structure is controlled by choosing crystalline feedstock withthe appropriate particle size distribution. In another embodiment,porosity characteristics are tailored by introducing pore-formers invarious ways and/or by refining a few of the processing stepsdownstream. With respect to ultrafiltration aspect of the inventivedual-purpose filter concept, in one embodiment, the porosity is about0.005 to about 0.25 microns at least on the very surface (membranelayer) of the filter. In another embodiment, the ultrafilterconfiguration includes a gradual porosity gradient from the surface ofthe filter to the interior. This can be achieved conveniently byfabricating a multi-layer pore structure. The macro-sized porosity canreside in the bulk (interior portion) and sub-micron or nano-pores atthe surface (exterior portion) with micropores in the region in between.

As mentioned earlier, the ceramic compositions as well as the bulkceramic structures made from them are stable up to high temperatures.This can be advantageous in many scenarios as is elucidated in thefollowing. Typically, in filtration applications, the pores of theceramic filter tend to get clogged over a period of time in service andmust be declogged or regenerated quickly to avoid down time duringfilter cleaning via conventional means such as back-pulsing, steamcleaning, vacuuming or by baking out the undesired material. However,because the ceramic compositions of the present invention are stable athigh temperatures, have very low thermal expansion and very high thermalshock resistance, and are good microwave absorbers, the ceramic filterscan potentially be regenerated in situ. A material's ability to absorbmicrowaves is dictated by its dielectric constant—materials with largedielectric constants are good absorbers of microwave energy. Materialswhich are microwave absorbers are well known in the art (e.g., EP420513-B1) and several [NZP] compositions are notable among them. Inparticular, Type (II) inventive compositions which are analogous toNa_(1+x)A₂ ^(VI)P_(3-x) ^(IV)Si_(x)O₁₂ (where value of ‘x’ is greaterthan 0) result in excellent microwave coupling, for values of x between1.0 and 2.2, and they also exhibit ultra low (or negative) coefficientof thermal expansion and good thermal shock resistance.

Thus, in one embodiment, a microwave non-absorbing bulk body housing themicrowave suscepting ceramic filter can be placed in a microwave and thefilter heated and unclogged. In yet another embodiment, the inventivecomposition of the ceramic filter has the ability to support catalyticoxidation of carbonaceous material in the presence of heat. As a result,the filter regeneration can take place at a relatively lower temperatureand the efficiency of the in-situ filter regeneration process is likelyto be significantly improved In yet another embodiment, as the ceramiccomposition is durable against environmental phenomenon and heat, theceramic filter could be regenerated using high temperature and highpressure steam without the concern of leaching of the antimicrobialelements.

The ceramic compositions and/or materials of the present invention canbe applied to applications other than biocidal or antimicrobialapplications but which require the characteristics of the ceramiccompositions of the present invention which are, but are not limited to,(1) compositional flexibility, (2) a crystalline ceramic structure; (3)excellent stability at extreme temperatures; (4) chemical inertness andnon-toxicity; (5) controlled concentration of an active element, such asa bioactive element or other such elements, introduced into the ceramicstructure by ionic-substitution; (6) custom-formability into variousparticle morphologies and as bulk objects, (7) controlled porosity ofthe ceramic object all through the bulk; (8) engineered properties formultifunctionality; and (9) other characteristics that would beunderstood by those skilled in the art such as, but not limited to,reduced weight, high strength and high toughness.

The following non-limiting examples are presented to explain the presentinvention in further detail.

EXAMPLES Synthesis of Biocidal Ceramic Compositions Example 1

As discussed earlier and depicted in the flow chart of FIG. 2, areaction-precipitation wet chemical method was used for synthesizing allthe substantially single-phase, crystalline [NZP]-type biocidalcompositions. Batch sheets and formulations were prepared first with theobjective of obtaining at least 250 gms. each of specific compositionsof Type (II) and Type (I), some of which are listed in Table 1. Thebatch formulations were based on the use of carbonate or hydroxide oroxide or nitrate reagents, or combinations thereof, and phosphatecompounds for the wet chemical synthesis approach.

TABLE 1 Bioactive Species, Sample Chemical Formula Amount XRD ResultsDesignation & Compositional Type (w %) (Nominal) BC12 CaZr₄P₆O₂₄(Non-inventive) 0 w % Single Phase BC15 Ca_(0.9)Ag_(0.2)Zr₄P₆O₂₄ (II)Ag⁺ (2.18) Single Phase BC16 Ca_(0.9)Cu_(0.1)Zr₄P₆O₂₄ (II) Cu²⁺ (0.65)Single Phase BC17 Ca_(0.9)Ag_(0.3)Zr₄P_(5.9)Si_(0.1)O₂₄ (II) Ag⁺ (3.23)Single Phase BC18 Ca_(0.9)Cu_(0.15)Zr₄P_(5.9)Si_(0.1)O₂₄ (II) Cu²⁺(0.97) Single Phase BN2 NaZr₂P₃O₁₂ (Non-inventive) 0 w % Single PhaseBN6 NaAg_(0.1)Zr₂P_(2.9)Si_(0.1)O₁₂ Ag⁺ (2.15) Single Phase

For example, for synthesizing a 250 gm. sample of the Type IIcomposition viz. Ca_(0.9)Ag_(0.2)Zr₄P₆O₂₄, stoichiometric amounts of thefollowing raw materials—calcium hydroxide [Ca(OH)₂], or alternatively,calcium carbonate [CaCO₃], silver carbonate [Ag₂CO₃], colloidal zirconia(ZrO₂), or alternatively, zirconium oxynitrate [ZrO(NO₃)₂)]—were addedto controlled amounts of deionized water and vigorously mixed using aroll-mill or a paint-shaker. After mixing, the aqueous dispersion ofreactant mixture, containing all except the phosphate species, wasplaced in a large 2000 mL beaker and kept stirred. While being stirred,warm phosphoric acid (at about 35° C. to 40° C.) was added to thereactant mixture slowly. As a result of reaction between the reactantmixture and phosphate species, precipitates begin to form. Theprecipitation process is typically slightly exothermic and is completedwithin 10 minutes of starting the reaction.

The resulting precipitates are filtered and dried in an oven between 90°C. and 100° C. for 24 hrs. or until dried. After drying, theprecipitates containing the [NZP]-type precursors were placed in a cleanceramic crucible and calcined at a temperature between 900° C. and 1200°C. depending on the intended inventive composition. Up to 6 hrs. ofisothermal hold at maximum temperature is needed to complete theformation of crystalline, single-phase [NZP] biocidal composition. Thecalcined composition which essentially is in a powder form was thensubjected to analysis using X-ray diffraction and particle densitymeasurements to verify the crystallinity and purity of the [NZP] phase.

Antimicrobial Testing of Powders of the Ceramic Compositions Example 2

The general test procedure for antimicrobial testing of the inventivepowder samples consisted of the following steps. Phosphate BuffetedSaline (PBS) was diluted to 1× concentration (11.9 mM phosphates, 137 mMsodium chloride and 2.7 mM potassium chloride) to make 400 mL. To 200 mLof the 1×PBS, 2 g nutrient broth was added and dissolved. Test tubeswere filled with 9 mL PBS with nutrient broth and about 10 mg of eachNZP powder. Each powder was tested in duplicate. Additionally, two testtubes were used without any powder. The last two tubes acted as apositive control. All tubes were capped and autoclaved at 121° C. for 30minutes. After the test tubes had cooled to room temperature, 1 mL of10⁻² dilution Munoz XL-1 inoculum was added to each tube with NZPpowders as well as the positive control. All solutions were vortexed for60 seconds to mix before incubating at 32° C. for about 55 hrs. Samplesof each tube were then checked for bacteria using an Oxoid dipslide.

Powders of the ionically-substituted, antimicrobially-active [NZP]-typeceramic compositions were tested for antimicrobial properties by WasteManagement Research Center (WMRC) in Illinois. Five different inventivecompositions of Type (I) and two compositions of Type (II) weresubjected to this testing. Type (I) ceramic compositions were designatedas BC12, BC15, BC16, BC17 and BC18. Relevant Type (II) compositions weredesignated as BN2 and BN6. Of the above ceramic compositions, BC12 (alsocalled BC0) and BN2 (same as BN0) had no bioactive dopants in the[NZP]-type structure, whereas, BC15 through BC18 had slightly differentconcentrations of bioactive elements, i.e., silver (Ag) and copper (Cu).Table 1 provides details of the designation, chemical formula, weightpercent of bioactive element and in each of the single-phase, ceramiccompositions.

At first, calcined and crystalline powders of the Type (II) compositionswere tested using powder concentrations of 1 g/L in a nutrient richmedium. The inventive composition ofinterest—NaAg_(0.1)Zr₂P_(2.9)Si_(0.1)O₁₂—designated as BN6 in Table 1was estimated to show a log kill effectiveness of greater than 5 and,possibly, up to 8. In contrast, extensive growth was seen in thepositive controls and in tubes with undoped ceramic powders BN2 asclearly shown in the picture of FIG. 3.

Next, crystalline powders of the five (5) Type (I) compositions, as inTable 1, were tested for biocidal properties. Surprisingly, initialpowder testing of the d-CZP compositions for antimicrobial propertiesyielded log₁₀ microbe reduction numbers that were not conclusive.However, after modification of the powder-testing protocol to use ahigher concentration (10 mg/mL instead of 1 mg/mL used for the Type (II)powder testing) of the Type (I) powders in the organism-containingbroth, the results showed no bacterial growth in tubes containingpowders labeled BC15 and BC17 suggesting pronounced biocidal activity.The estimated log₁₀ reduction based on CFU/ml measurements was >4.0and >5.0, respectively for BC15 and BC17 ceramic compositions.Composition BC18 exhibited some biocidal activity with bacterial countsof 10⁵CFU/nL compared to a positive control which had 10⁷ CFU/mL.

Preparation of Bulk Test Samples of Ceramic Compositions Example 3

In order to make small tile samples for antimicrobial testing, 125 gms.of each of the calcined powders of the inventive ceramic compositionswith substantially, single-phase [NZP] characteristics were dry milledin a paint-shaker with 1 to 2 wt % (based on solids) of PEG-8000 organicsolid binder in a clean HDPE (Nalgene) plastic bottle. To facilitatedeagglomeration of the calcined composition(s) and to ensure good mixingof the binder with the particles of the ceramic powder, zirconiagrinding media weighing roughly four (4) times the mass of the ceramicpowder was used and milling was done for at least 15 minutes and up to30 minutes at a maximum.

The milled ceramic compositions containing the PEG binder were screeneddry through a −325 mesh screen to remove any remnant agglomerates. Usingroughly 40 gms. of the screened powder, a 2.0 inch (about 5 cm)×2.0 inch(about 5 cm) square tile was formed by uniaxially compressing the powderat 15 MPa in a single-action Carver die press and thenisostatically-pressing the tile at 210 MPa. For each of the inventivebiocidal ceramic composition, two tile samples were die and iso-pressed,followed by sintering at temperatures between 1400° C. and 1500° C.(depending on composition) for 4 hours.

Prior to machining the sintered tiles to appropriate sizes forconducting antimicrobial assay tests at an accredited laboratory, thetile samples were checked for physical integrity and subjected todensity testing per ASTM standard. Another key check that was conductedinvolved observation of color of each of the test tiles. A uniformlywhite tile (regardless of the bioactive dopant) is usually a good firstindicator of having achieved substantially single-phase, crystalline[NZP] compositional characteristics.

Testing of Bulk Samples of Ceramic Compositions Example 4

A modified AATCC antimicrobial assay was employed by NELSON Labs in SaltLake City to determine the biocidal properties of the inventive ceramiccompositions to be screened. Test samples were die-pressed, sintered,and machined into 1 inch square (about 6.25 cm²) tiles of the respectivecomposition. A proprietary protocol based on inoculating coupons of thetest material with the test organism, then determining the percentreduction of the test organism after a specified exposure period wasestablished and followed.

At first, Salmonella cholerasuis cultures were grown in soybean caseindigest broth (SCDB) media at an incubation temperature of 37.5° C. forbetween 24 and 48 hours. The bacterial cultures were vortexed thoroughlyto remove agglomerates or clumps, and filtered through gauze. Theinoculum was also frequently mixed to ensure uniform distribution ofchallenge. The concentration of the microbial suspensions was adjustedusing PEPW to produce a uniform challenge level of approximately10⁶CFU/mL using visual turbidity.

Prior to test sample inoculation, extraction from uninoculatedantimicrobial sample was done in 100 mL aliquots of LETH. To this,approximately 1000 to 10000 CFU of the test organism mix was added andthe aliquots plated onto Soybean Casein Digest Agar (SCDA) intriplicate. To confirm the titration of the diluted test organism on theappropriate media, the same volume of inoculum (1000 to 10000 CFU) wasadded to a 100 mL bottle of LETH. The aliquots were then plated on toSCDA in the same manner. All plates were then incubated at 37.5° C. for48 to 72 hours. The goal of this procedure was to demonstrate at least70% recovery or 10 to 100 CFU of the organism.

Roughly 1.0 mL of the challenge organism (about 10⁶ CFU) was placed onthe surface of each sample coupon using a pipette. Coupons of all theantimicrobial [NZP]-type compositions as well as untreated baselinematerials were tested. The inoculated samples were placed in a closedcontainment vessel at approximately 37.5° C. for predetermined time(s).At the end of each incubation time interval, the inoculated sample wasplaced in a flask containing 100 mL of LETH and the flask shakenmanually for 1 minute. A plate count (in triplicate) was done using anappropriate aliquot evenly spread on SCDA plates with a sterile bentglass rod (NL1 SOP/MBG/003). This test was done at 0 and 24 hours forthe baseline controls and at 24 hours for the antimicrobial materials.For the 24 hr. test, the bacteria laden sample plates were incubated at37.5° C. for the duration.

Two neutral controls viz. ‘gauze’ (primary control), which facilitatesthe natural growth of bacteria under neutral environmental conditionsand ‘dry wall’ (secondary control) were employed for natural bacteriamortality rates. In addition to the two protocol controls, coupons ofthe baseline undoped compositions were also utilized in the study. Forthe same testing, as discussed earlier, other positive and negativecontrols were also utilized. A 100 mL bottle of LETH served as thenegative control while the 100 mL bottle of LETH spiked with thechallenge organism was the positive control.

Results were calculated in terms of percent reduction of the microbialorganism in terms of ‘Colony Forming Units’ (CFU/sample). The followingformula is utilized: [(C−A)/C]×100=R (% Reduction) where ‘A’ is thenumber (counts) of organisms recovered from the inoculated testspecimens and ‘C’ is the corresponding number from the inoculatedcontrol samples immediately after inoculation (time ‘t’=0 hrs.). Table 2below summarizes the results obtained from the antimicrobial testing ofthe inventive ceramic compositions as compared to passive controls.

TABLE 2 Exposure Average Control Average Percent Log₁₀ Sample IDIntervals (hr) Titer at t = 0 (CFU) Recovered (CFU) Reduction ReductionGauze 0 8.20E+07 8.20E+07 0 0 Control 24 8.20E+07 7.00E+08 −750 −0.93Dry Wall 0 8.70E+07 8.70E+07 0 0 Control 24 8.70E+07 3.70E+07 58 0.37BC0/BC12 24 8.70E+07 2.90E+05 99.666 2.48 BC15 24 8.70E+07<200 >99.99977 >5.64 BC16 24 8.70E+07 6.60E+03 99.9924 4.12 BC17 248.70E+07 <200 >99.99977 >5.64 BC18 24 8.70E+07 <200 >99.99977 >5.64BN0/BN2 24 8.80E+07 <200 >99.99977 >5.64 BN6 24 8.80E+07 <200 >99.99977>5.64

Almost all bulk test samples (except BC16) from the inventivecompositions showed >5.0 log kill values with respect to Salmonellabacteria. The test samples had a 30% greater kill rate (99.99977%) thanthe dry wall, while the gauze control aided bacterial growth whichresulted in a population increase of an entire order of magnitude. Theseresults (bacterial population change and log reduction values) have beenpresented in Table 2 and the antimicrobial activity plot of FIG. 4. Theexceptional antimicrobial properties of all but one of the inventivecompositions against Salmonella Choleraesils and (by scientificdeduction) Escherichia Coli is, thus, evident. Surprisingly, the undoped[NZP] composition (BN-0) also showed higher than expected levels ofbiocidal activity arising as a result of its “phosphate” chemistry. Anymechanisms that would explain such high intrinsic activity requirefurther studying.

Example 5

Following the demonstration of the excellent antimicrobial properties ofthe inventive biocidal ceramic compositions, leaching tests wereconducted to evaluate the physical and chemical stability of the samecompositions in hot aqueous and mild acid environments. The primaryintent was to evaluate resistance to water-enhanced leaching of the bulktile samples after a 12 hour soak in boiling water (about 100° C.).

A small coupon sample of each of the compositions listed in Table 1 wasfirst weighed and then immersed in boiling water for 12 hours. After thesoak period, the coupons were thoroughly dried and then weighed again todetermine if there was any weight loss (a manifestation of leaching). Ascan be inferred from the data in Table 3, most of the tested samplessurvived the test unscathed with no signs of leaching; while a couple ofthe samples (BC12 and BN2) exhibited small but measurable weightlosses—which was confirmed by the presence of trace amounts of sedimentsin the water. In conclusion, it can be stated that in spite of thefairly high degree of porosity (33% to 45%) of the leaching testsamples, the majority of the [NZP]-type, ceramic compositions areremarkably resistant to leaching in boiling water (H₂O) in spite oftheir porous nature.

TABLE 3 Sample Mass (g) Mass (g) Density % Weight Designation Pre-TestPost-Test (g/cc) % Dense Loss BC12 6.53 6.51 2.018 62.48 0.31 BC15 7.187.173 2.140 66.46 0.12 BC16 7.36 7.34 1.925 61.11 0.27 BC17 10.19 10.182.117 65.78 0.09 BC18 4.64 4.633 1.976 62.70 0.15 BN2 7.21 7.19 1.73554.22 0.42 BN6 7.36 7.36 1.808 55.90 0.00

The sample coupons which were subjected to leaching test and,subsequently, dried for about 24 hours under a halogen lamp or undernatural sunlight exhibited no color change. Samples of the inventivecompositions retained their color regardless of the ambient condition.This not only attests to the chemical-binding of the bioactive speciesin the single phase, [NZP]-type structure of the inventive compositionsbut also demonstrates the excellent discoloration resistance inherent tosuch ceramic formulations.

The present invention may be embodied in other specific forms withoutdeparting from its spirit or essential characteristics. The describedembodiments are to be considered in all respects only as illustrativeand not restrictive. Moreover, the invention disclosed in detail hereincan be defined with other claims, including those that will be includedin any related non-provisional applications that will be filed duringthe pendency of this patent application.

1. A method for preparing a biocidal ceramic composition represented bythe following general chemical formula:M¹ _(1-x-1y-mz)M² _(kx)Zr^(VI) _(4-y)A_(y)P^(IV) _(6-z)B_(z)O₂₄ whereinM¹ is at least one divalent alkaline earth cation; wherein M² representsionic-substitution of the M¹ sites, wherein M² is at least onebio-active cation; wherein 0≦x≦1; wherein 0≦y≦4; wherein 0≦z≦6; whereink=1 if M² is a divalent cation; wherein k=2 if M² is a monovalentcation; wherein A represents ionic-substitution of Zr (zirconium) sites,wherein 1=0.5 if A is pentavalent cation; wherein 1=0 if A istetravalent cation; wherein 1=−0.5 if A is trivalent cation; wherein Brepresents ionic-substitution of P (phosphorus) sites, wherein m=0.5 ifB is hexavalent cation; wherein m=0 if B is pentavalent cation; whereinm=−0.5 if B is tetravalent cation; and wherein m=−1 if B is trivalentcation, the method comprising: a) mixing together the followingprecursors to form a mixture: i) a compound of an alkaline earth metal;ii) a compound of a dopant selected from a group consisting of H, Ag,Cu, Ni, Zn, Mn, Sn, Co, and combinations thereof; iii) a zirconium ionsource; and iv) a phosphorus ion source; b) drying at least some of aproduct that forms from the mixture in air between about 50° C. to about150° C. until dried; and c) calcining the dried mixture between about750° C. to about 1200° C. for about 5-10 hours.
 2. The method accordingto claim 1, wherein mixing together the precursors of claim 1 to form amixture comprises: adding the precursors identified in i), ii), and iii)to controlled amounts of a liquid medium to form a first mixture andvigorously mixing the first mixture; adding the precursor identified iniv) to the first mixture resulting in precipitates forming from areaction of the first mixture and the phosphorus ion source; andfiltering the precipitates.
 3. The method according to claim 1, whereinmixing together the precursors of claim 1 to form a mixture comprises:adding the precursors identified in i), ii), and iii) to controlledamounts of a solvent to form a first mixture and vigorously mixing thefirst mixture; adding controlled amounts of a colloidal silicon sourceto the first mixture; adding the precursor identified in iv) to thesilicon source and the first mixture resulting in a gel forming from thereaction of the colloidal silicon source, the first mixture, and thephosphorus ion source.
 4. The method according to claim 1, furthercomprising, prior to drying at least some of the product that forms fromthe mixture, treating the product hydrothermally under controlled pHconditions.
 5. The method according to claim 1, wherein the dopantcomprises 0.0001% to 20% of a total mass of the resulting biocidalceramic composition.
 6. The method according to claim 1, wherein atleast one of: the alkaline earth metal is selected from a groupconsisting of Ca, Mg, Sr, Ba, and combinations thereof; the zirconiumion source is selected from a group consisting of ZrOCl₂.xH₂O,ZrO(NO₃)₂.xH₂O, (ZrCO₃)₂.H₂O and combinations thereof; or the phosphorusion source selected from a group consisting of NH₄H₂PO₄, H₃PO₄,(NH₄)₂HPO₄, and combinations thereof.
 7. The method according to claim1, wherein the compound of at least one of the precursors identified ini), ii) or iii) is introduced into the mixture as an at least partiallysoluble compound selected from the group consisting of a carbonate,nitrate, acetate, or hydroxide.
 8. The method according to claim 1,wherein mixing together the precursors of claim 1 to form a mixturefurther comprises at least one of: introducing a compound of dopantselected from a group consisting of Nb, Ta, V, Ti, Hf, Y, Sc, andstoichiometric combinations thereof; to perform ionic substitution ofthe Zr (zirconium) site; or introducing a compound of dopant selectedfrom a group consisting of S, As, Si, Ge, Al, or B, and stoichiometriccombinations thereof, to perform ionic substitution of the P(phosphorus) site.
 9. A method for preparing a biocidal ceramiccomposition represented by the following general chemical formula:M¹ _(1-x-1y-mz)M² _(kx)Zr^(VI) _(4-y)A_(y)P^(IV) _(6-z)B_(z)O₂₄ whereinM¹ is at least one divalent alkaline earth cation; wherein M² representsionic-substitution of the M¹ sites, wherein M² is at least onebio-active cation; wherein 0<x≦1; wherein 0≦y≦4; wherein 0≦z≦6; whereink=1 if M² is a divalent cation; wherein k=2 if M² is a monovalentcation; wherein A represents ionic-substitution of Zr (zirconium) sites,wherein 1=0.5 if A is pentavalent cation; wherein 1=0 if A istetravalent cation; wherein 1=−0.5 if A is trivalent cation; wherein Brepresents ionic-substitution of P (phosphorus) sites, wherein m=0.5 ifB is hexavalent cation; wherein m=0 if B is pentavalent cation; whereinm=−0.5 if B is tetravalent cation; and wherein m=−1 if B is trivalentcation, the method comprising: a) mixing in a dry state a stoichiometricmixture of the following precursors to form a solid-state mixture: i) azirconate of alkaline-earth metal; ii) at least one of an oxide,carbonate, acetate, hydroxide or nitrate of a dopant selected from agroup consisting of H, Ag, Cu, Ni, Zn, Mn, Sn, or Co, and combinationsthereof; and iii) a zirconium source; and iv) a phosphorus source; andb) calcining the solid-state mixture between about 750° C. to about1200° C. for about 5-10 hours.
 10. The method according to claim 9,wherein at least one of: the zirconate of alkaline-earth metal isselected from a group consisting of Ca, Mg, Sr, Ba, and combinationsthereof; or the zirconium source and the phosphorus source are comprisedof zirconium pyrophosphate (ZrP₂O₇).
 11. The method according to claim9, wherein mixing in a dry state a stoichiometric mixture of thefollowing precursors to form a solid-state mixture comprises at leastone of: mixing the precursors in at least one of a mortar and pestle, ora mill with ceramic grinding media; or mixing a silicon source in a drystate in the mixture.
 12. The method according to claim 9, wherein thedopant comprises 0.0001% to 20% of a total mass of the resultingbiocidal ceramic composition.
 13. The method according to claim 9,wherein at least one of: the zirconium (Zr) site is substituted byadding to the mixture a compound of a dopant selected from a groupconsisting of Nb, Ta, V, Ti, Hf, Y, Sc, and stoichiometric combinationsthereof; or the phosphorus (P) site is substituted by adding to themixture a compound of a dopant selected from a group consisting of S,As, Si, Ge, Al, or B, and stoichiometric combinations thereof.
 14. Amethod for preparing a biocidal ceramic composition represented by thefollowing general chemical formula:M¹ _(1-x-1y-mz).M² _(kx)Zr^(VI) _(2-y)A_(y)P^(IV) _(3-z)B_(z)O₁₂ whereinM¹ is at least one monovalent alkali cation; wherein M² representsionic-substitution of M¹ sites, wherein M² is at least one bio-activecation; wherein 0≦x≦1; wherein 0≦y≦2; wherein 0<z≦3; wherein k=0.5 if M²is a divalent cation; wherein k=1 if M² is a monovalent cation; whereinA represents ionic-substitution of Zr (zirconium) sites, wherein 1=1when A is pentavalent cation; wherein 1=0 when A is tetravalent cation;wherein 1=−1 when A is trivalent cation; wherein B representsionic-substitution of P (phosphorus) sites, wherein m=1 when B ishexavalent cation; wherein m=0 when B is pentavalent cation; whereinm=−1 when B is tetravalent cation; and wherein m=−2 when B is trivalentcation, the method comprising: a) mixing together the followingprecursors to form a mixture: i) a compound of an alkali metal; ii) acompound of a dopant selected from a group consisting of H, Ag, Cu, Ni,Zn, Mn, Sn, Co, and combinations thereof; iii) a zirconium ion source;iv) a phosphorus ion source; and v) a compound of dopant selected from agroup consisting of S, As, Si, Ge, Al, or B, and stoichiometriccombinations thereof; to perform ionic substitution of the P(phosphorus) site; b) drying at least some of a product that forms fromthe mixture in air between about 50° C. to about 150° C. until dried;and c) calcining the dried mixture between about 750° C. to about 1200°C. for about 5-10 hours.
 15. The method according to claim 14, whereinmixing together the precursors of claim 14 to form a mixture comprises:adding the precursors identified in i), ii), and iii) to controlledamounts of a liquid medium to form a first mixture and vigorously mixingthe first mixture, wherein the precursor identified in v) is addedeither to the first mixture or subsequent thereto; adding the precursoridentified in iv) to the first mixture resulting in precipitates formingfrom a reaction of the first mixture and the phosphorus ion source; andfiltering the precipitates.
 16. The method according to claim 14,wherein mixing together the precursors of claim 14 to form a mixturecomprises: adding the precursors identified in i), ii), and iii) tocontrolled amounts of a solvent to form a first mixture and vigorouslymixing the first mixture, wherein the precursor identified in v) isadded either to the first mixture or subsequent thereto; addingcontrolled amounts of a colloidal silicon source to the first mixture;and adding the precursor identified in iv) to the silicon source and thefirst mixture resulting in a gel forming from the reaction of thecolloidal silicon source, the first mixture, and the phosphorus ionsource.
 17. The method according to claim 14, further comprising, priorto drying at least some of the product that forms from the mixture,treating the product hydrothermally under controlled pH conditions. 18.The method according to claim 14, wherein the dopant comprises 0.0001%to 20% of a total mass of the resulting biocidal ceramic composition.19. The method according to claim 14, wherein at least one of: thecompound of an alkali metal is selected from a group consisting of Li,Na, K, Rb, Cs, and combinations thereof; the zirconium ion source isselected from a group consisting of ZrOCl₂.xH₂O, ZrO(NO₃)₂.xH₂O,(ZrCO₃)₂.H₂O and combinations thereof; or the phosphorus ion sourceselected from a group consisting of NH₄H₂PO₄, H₃PO₄, and combinationsthereof
 20. The method according to claim 14, wherein the compound of atleast one of the precursors identified in i), ii) or iii) is introducedinto the mixture as an at least partially soluble compound selected fromthe group consisting of a carbonate, nitrate, acetate, or hydroxide. 21.The method according to claim 14, wherein mixing together the precursorsof claim 25 to form a mixture further comprises introducing a compoundof dopant selected from a group consisting of Nb, Ta, V, Ti, Hf, Y, Sc,and stoichiometric combinations thereof, to perform ionic substitutionof the Zr (zirconium) site.
 22. A method for preparing a biocidalceramic composition represented by the following general chemicalformula:M¹ _(1-x-1y-mz).M² _(kx)Zr^(VI) _(2-y)A_(y)P^(IV) _(3-z)B_(z)O₁₂ whereinM¹ is at least one monovalent alkali cation; wherein M² representsionic-substitution of M¹ sites, wherein M² is at least one bio-activecation; wherein 0≦x≦1; wherein 0≦y≦2; wherein 0<z≦3; wherein k=0.5 if M²is a divalent cation; wherein k=1 if M² is a monovalent cation; whereinA represents ionic-substitution of Zr (zirconium) sites, wherein 1=1when A is pentavalent cation; wherein 1=0 when A is tetravalent cation;wherein 1=−1 when A is trivalent cation; wherein B representsionic-substitution of P (phosphorus) sites, wherein m=1 when B ishexavalent cation; wherein m=0 when B is pentavalent cation; whereinm=−1 when B is tetravalent cation; and wherein m=−2 when B is trivalentcation, the method comprising: a) mixing in a dry state a stoichiometricmixture of the following precursors to form a solid-state mixture: i) analkali metal source; ii) at least one of an oxide, carbonate, acetate,hydroxide or nitrate of a dopant selected from a group consisting of H,Ag, Cu, Ni, Zn, Mn, Sn, or Co, and combinations thereof; and iii) azirconium source; iv) a phosphorus source; and v) a dopant selected froma group consisting of S, As, Si, Ge, Al, or B, and stoichiometriccombinations thereof, to perform ionic substitution of the P(phosphorus) site; b) calcining the solid-state mixture between about750° C. to about 1200° C. for about 5-10 hours.
 23. The method accordingto claim 22, wherein at least one of: the alkali metal source isselected from a group consisting of Li, Na, K, Rb, Cs, and combinationsthereof; or the zirconium source and the phosphorus source are comprisedof zirconium pyrophosphate (ZrP₂O₇).
 24. The method according to claim22, wherein mixing in a dry state a stoichiometric mixture of thefollowing precursors to form a solid-state mixture comprises at leastone of: mixing the precursors in at least one of a mortar and pestle, ora mill with ceramic grinding media; or mixing a silicon source in a drystate in the mixture.
 25. The method according to claim 22, wherein thedopant comprises 0.0001% to 20% of a total mass of the resultingbiocidal ceramic composition.
 26. The method according to claim 22wherein the zirconium (Zr) site is substituted by adding to the mixturea compound of a dopant selected from a group consisting of Nb, Ta, V,Ti, Hf, Y, Sc, and stoichiometric combinations thereof.